Why NAD+ Drops With Age And What The Science Says About NMN And NR

Send us Fan MailWe track the real biology behind the NAD+ craze, from how cells turn food into energy to why that energy system breaks down with age. We also weigh what NMN and NR actually do in human trials against what marketing claims they do, including the messy roles of CD38 and the gut microbiome. • NAD+ as an electron carrier that powers ATP production • Mitochondrial dysfunction as NAD+ declines with age • Sirtuins as NAD+-dependent regulators of repair and stress responses • Why “sirtfood” claims collapse on dose and bioavailability • The failed PARP1 explanation and the disposable soma theory • CD38 as an NADase that rises with age • Knockout and overexpression studies that point to causation • Why oral NAD+ cannot raise intracellular NAD+ directly • NR and NMN as precursors using salvage pathways and transporters • CD38 degrading precursors in vivo and acting as an ectoenzyme • What 2025–2026 human clinical trials show on safety and biomarkers • Muscle biopsy paradox of unchanged steady-state NAD+ • Metabolic flux, species differences, and why humans are not mice • Microbiome conversion of NR into niacin and the NAAD signal • Conflicts of interest, surrogate markers versus real clinical endpoints • Supplement purity problems and the theoretical cancer-fueling risk • Why CD38 inhibitors may be a better long-term target than higher dosing This podcast is created by Ai for educational and entertainment purposes only and does not constitute professional medical or health advice. Please talk to your healthcare team for medical advice. Never miss an episode—subscribe on your favorite podcast app!